Sandbox Reserved 595: Difference between revisions

ApoE proteins self-associate in order to form dimers, tetrameters, and higher aggregates.  These phenomena occur in a concentration, pH, and temperature-dependent manner '<ref>Gau et al. 2011.  Mass spectrometry-based protein foot printing characterizes the structures of oligomeric apolipoprotein E2, E3, and E4.  Biochemistry 50(38):8117-26.</ref>'.  Oligomerization also correlates with the length of the C-terminal domain '<ref>Chou, Chi-Yuan. et al.  2005. Structural Variation in Human Apolipoprotein E3 and E4: Secondary Structure, Tertiary Structure, and Size Distribution. Biophysical Journal 88:455–466.</ref>'.  Resulting from this protein's propensity to aggregate is difficulty in determining the full-length three-dimensional structure '<ref>Richard, UC et al.  2011. Hydrogen/Deuterium Exchange and Electron-Transfer Dissociation Mass Spectrometry Determine the Interface and Dynamics of Apolipoprotein E Oligomerization.  Biochemistry 50(43):9273-82.</ref>'.  At μM concentrations, ApoE primarily exists as a tetrameter.  When members of a tetrameter dissociate, the subsequent dimeric and monomeric forms retain their structure; dissociation from a tetrameter may serve to open new ligand binding sites (Q).

Familial Type III hyperlipoproteinemia is a genetic lipid disorder that is marked by an increase in the concentrations of plasma cholesterol and triglyceride levels (Rall 82).  Normally, in individuals whose apoE is functional, chylomicron remnants and VLDL remnants are rapidly removed from circulation via recptor-mediated endocytosis within the liver.  However, this condition develops as a result of apoE that has impaired clearance abilities.  When a defect in apoE of this nature is present, delayed clearance in the plasma of triglyceride-rich lipoprotein remants results; significantly elevated levels of cholesterol-encriched remnant lipoproteins are a defining feature of this disorder '<ref>OMIM.Omim.org/entry/107741.</ref>' (Kashyap).  Individuals homozygous for the ε2 allele are most susceptible.  The E2 isoform of apoE exhibits weak or defective binding of remnants to hepatic lipoprotein receptors; the E2 isoform also clears these remnants from the plasma in a sluggish fashion '<ref>OMIM.Omim.org/entry/107741.</ref>'.